Risk Factors for Alzheimer's Disease Among Latinos: Relationships Between Cardiovascular Disease Risk, Acculturation, Small Vessel Disease, and Alzheimer's Biomarkers - PROJECT SUMMARY Latinos/as are a large and growing segment of the United States older adult population and are at increased risk for Alzheimer’s disease and related dementias (ADRDs) compared to non-Latino/a Whites. Evidence suggests that Latinos/as are particularly susceptible to ADRD in the presence of cardiovascular disease risk factors (CVDRFs). Several other factors (e.g., sex, acculturation, Alzheimer’s biomarkers) may influence the degree to which CVDRFs are linked to ADRD risk. For example, our own preliminary data suggest that Latina women with elevated CVDRFs are more likely to have mild cognitive impairment (MCI), an intermediate stage between healthy cognition and ADRD, than men. Interestingly, less acculturation (i.e., maintaining Latino/a culture and less adoption of Anglo-American culture) has been associated with better cardiovascular health, particularly among women, but pilot data has linked lower acculturation to poorer cognition. Finally, Alzheimer’s biomarkers are becoming more accessible but have not been thoroughly investigated among Latinos/as who are more likely to have mixed Alzheimer’s and cerebrovascular pathology (brain damage linked to poor cardiovascular health) as opposed to pure Alzheimer’s pathology. The overarching goal of the proposed study is to develop a comprehensive characterization of cognitive impairment and ADRD risk among middle-age and older Latinos/as. To achieve this, the proposed project will incorporate psychosocial (i.e., acculturation) and biological [i.e., CVDRFs, small vessel disease (a marker of cerebrovasculature), and Alzheimer’s biomarkers] factors to study longitudinal cognitive change among Latinos/as 50+ years old. More specifically, the proposed project will examine detailed cognitive data from the Study of Latinos- Investigation of Neurocognitive Aging (SOL-INCA), SOL-INCA MRI (magnetic resonance imaging), and SOL-INCA AD (Alzheimer’s disease), ancillary studies to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). In aim 1 we seek to characterize gender-specific associations between acculturation and MCI, and test if CVDRFs underly the link between acculturation and MCI status in over 6,000 Latinos/as. In aim 2 we will use gender-specific analysis to determine if small vessel disease accounts for the relationship between CVDRFs and MCI/dementia status (while accounting for acculturation); projected n = 2,400. In aim 3, we will examine whether acculturation or Alzheimer’s biomarkers influence the relationships between small vessel disease and MCI/dementia status; projected n = 2,400. The proposed K08 project will provide the candidate the tools necessary to continue investigating Latino/a cognitive aging and ADRD risk through the National Institute on Aging’s Health Disparities Framework as an independent clinical scientist.